In recent years, medical oxygen regulators that incorporate a cylinder isolation valve have increased in popularity. These devices, often called valve-integrated pressure regulators (VIPRs), essentially combine several components into one highly compact manifold design, typically including a fill valve, shut-off valve, residual pressure valve, regulator, and relief valve. Combining these components into a single manifold block presents unique oxygen fire hazards that can differ greatly from those found in the stand-alone versions of the components. In order to avoid fires, these hazards must be understood and addressed in the design of the VIPR. This paper presents the most common oxygen fire hazards found in VIPR devices as well as the ASTM analysis and testing methods used to qualify a new design, specifically considering oxygen compatibility of materials, toxicity of combustion products, ignition mechanisms, and reaction effects of a fire.